Sorafenib in Treating Patients With Advanced or Metastatic Cancer of the Urinary Tract

Stage IV Bladder Cancer Clinical Trial

Official title:

A Phase II Study of BAY 43-9006 in Advanced or Metastatic Urothelial Cancer (Transitional Cell Cancer of the Bladder, Ureter and Renal Pelvis)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00112671
• Other study ID #: NCI-2012-03095
• Secondary ID: PHL-0367062N01CM
• Status: Completed
• Phase: Phase 2
• Start date: April 2005
• Est. completion date: May 2010

Study information

• Verified date: July 2018
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial is studying how well sorafenib works in treating patients with advanced or metastatic cancer of the urinary tract. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

Description:

PRIMARY OBJECTIVES:

I. To assess the efficacy (response rate and stable disease rate) of Bay 439006 given to patients with advanced or metastatic urothelial cancer.

II. To assess the toxicity, time to progression and response duration of Bay 439006 given to patients with advanced or metastatic urothelial cancer.

III. To measure Ras mutational status and EGFR/HER2 on archival specimens. To determine baseline and post-treatment levels of pERK, pAKT, VEGFR2, CD31, Ki-67/MIB-1, and cleaved caspase 3 and to explore the relationship between these correlative endpoints and clinical outcome.

OUTLINE: This is a nonrandomized, open-label, multicenter study.

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed within 3 weeks and then every 3 months thereafter.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed transitional cell cancer of the bladder, renal pelvis or ureter

• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan

• Patients must not have had any prior systemic therapy for advanced or metastatic disease; prior adjuvant or neoadjuvant chemotherapy is permitted providing it was completed at least 4 weeks prior to study entry; radiation therapy is permitted if completed > 4 weeks prior to trial entry

• Life expectancy of greater than 3 months

• ECOG performance status 0 or 1 (Karnofsky >= 70%)

• Leukocytes >= 3,000/uL

• Absolute neutrophil count >= 1,500/uL

• Platelets >= 100,000/uL

• Total bilirubin within normal institutional limits

• AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal

• Creatinine < 1.5 x ULN OR creatinine clearance >= 45 mL/min/1.73 m^2

• No serious medical conditions such as myocardial infarction within 6 months prior to entry, congestive heart failure, unstable angina, active cardiomyopathy, unstable ventricular arrhythmia, uncontrolled hypertension, uncontrolled psychotic disorders, serious infections, active peptic ulcer disease, or any other medical conditions that might be aggravated by treatment

• Patients must have tumor lesions accessible for biopsy for correlative studies and must be willing to undergo tumor biopsy once before and once during experimental therapy; if there is a medical contraindication to biopsy, exception may be granted upon discussion with the Principal Investigator/Chair

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

• Able to swallow and retain oral medication

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Prior systemic therapy for advanced or metastatic urothelial carcinoma

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents

• Patients receiving any other investigational agents, or concurrent anticancer therapy

• Patients with only non-measurable disease, defined as all other lesions, including small lesions (longest diameter < 20mm with conventional techniques or < 10 mm with spiral CT scan) and truly non-measurable lesions, which include the following:

• Bone lesions

• Leptomeningeal disease

• Ascites

• Pleural/pericardial effusion

• Inflammatory breast disease

• Lymphangitis cutis/pulmonis

• Abdominal masses that are not confirmed and followed by imaging techniques

• Cystic lesions

• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound evaluation of neurologic and other adverse events

• Patients with a history of other active malignancy in the past 5 years (with the exception of adequately treated cervical carcinoma in situ and non melanomatous skin cancers) are excluded

• Uncontrolled intercurrent illness including, but no limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Patients must not have any evidence of a bleeding diathesis

• Patients must not be on therapeutic anticoagulation; prophylactic anticoagulation (ie. Low dose warfarin) of venous or arterial access devices is allowed provided that the requirements for PT, INR or PTT are met

• Patients must not be taking the cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine, or Phenobarbital), rifampin or St. John's Wort

• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with BAY 43-9006

• Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to BAY 43-9006

• Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis)

Related Conditions & MeSH terms

• Carcinoma, Transitional Cell
• Kidney Neoplasms
• Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter
• Recurrent Bladder Cancer
• Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter
• Regional Transitional Cell Cancer of the Renal Pelvis and Ureter
• Stage III Bladder Cancer
• Stage IV Bladder Cancer
• Transitional Cell Carcinoma of the Bladder
• Ureteral Neoplasms
• Urinary Bladder Neoplasms

Intervention

Drug:
• sorafenib tosylate
Given orally 400mg orally twice daily

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
Canada	Princess Margaret Hospital Phase 2 Consortium	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Paricipants With Tumour Response Defined as Partial or Complete Response Per the RECIST 1.0 Criteria	Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least 30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR.	Up to 5 years
Secondary	Number of Participants With Stable Disease for More Than 3 Months	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), >=20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.	From the start of the treatment until the criteria for progression are met, up to 5 years
Secondary	Time to Progression	Progression is defined using the Response Evaluation Criteria In Solid Tumours Criteria (RECIST v1.0) as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in non-target lesions, or the appearance of new lesions.	Up to 5 years
Secondary	Progression-free Survival	Summary statistics, such as the mean, median, counts and proportion, will be used to summarize the patients. Survival estimates will be computed using the Kaplan-Meier method. Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon tests may be substituted if necessary. 95% confidence intervals will be constructed and selected results will be illustrated.	From start of treatment to progression or death, assessed up to 1 year
Secondary	Frequency of Common Grade 3 Adverse Events	Will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest.	Up to 5 years